engleski

Theoretical Study on the Enantioselective Epoxide Ring Opening by Halohydrin Dehalogenase from Arthrobacter sp.

Halohydrin dehalogenases (HheA, HheB and HheC) were found to efficiently catalyse nucleophilic ring opening of epoxides with high regioselectivity opposite to the regioselectivity of the nonenzymatic epoxide- opening. Activity, enantioselectivity and enantiopreference depend on the type of enzyme and the substrate structure.1 The epoxide- opening reaction of halohydrin dehalogenase HheA from Arthrobacter sp.2 was investigated theoretically in order to understand the observed enantiopreference toward chiral epoxides and to predict possible structural changes to further improve selectivity. The cyanolysis and azidolysis of a series of mono- and disubstituted epoxides (Sheme 1) within the active site of HheA were studied using AutoDock 4.2.2 suite of programs.3 Lamarckian Genetic Algorithm (LGA) search method was employed and geometries of the enzyme-epoxide complexes were calculated. The results obtained by docking simulations were in a good agreement with the experimentally available data. Analyses of structures showed that the regioselectivity and enantiopreference of the enzymatic epoxide opening is influenced by a combination of steric and electrostatic factors. Distribution of hydrogen bonds in the active site is very important and controls motion of the substrate and the nucleophile. The difference in orientations and relative energies of the productive and non-productive binding will be presented and discussed.

Halohydrin dehalogenase A ; epoxides ; enantioselectivity

nije evidentirano